Browsing by Subject "Early diagnosis"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease
    (American Medical Association, 2021) Janelidze, Shorena; Berron, David; Smith, Ruben; Strandberg, Olof; Proctor, Nicholas K.; Dage, Jeffrey L.; Stomrud, Erik; Palmqvist, Sebastian; Mattsson-Carlgren, Niklas; Hansson, Oskar; Neurology, School of Medicine
    Importance: There is an urgent need for inexpensive and minimally invasive blood biomarkers for Alzheimer disease (AD) that could be used to detect early disease changes. Objective: To assess how early in the course of AD plasma levels of tau phosphorylated at threonine 217 (P-tau217) start to change compared with levels of established cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers of AD pathology. Design, setting, and participants: This cohort study included cognitively healthy control individuals (n = 225) and participants with subjective cognitive decline (n = 89) or mild cognitive impairment (n = 176) from the BioFINDER-2 study. Participants were enrolled at 2 different hospitals in Sweden from January 2017 to October 2019. All study participants underwent plasma P-tau217 assessments and tau- and amyloid-β (Aβ)-PET imaging. A subcohort of 111 participants had 2 or 3 tau-PET scans. Main outcomes and measures: Changes in plasma P-tau217 levels in preclinical and prodromal AD compared with changes in CSF P-tau217 and PET measures. Results: Of 490 participants, 251 were women (51.2%) and the mean (SD) age was 65.9 (13.1) years. Plasma P-tau217 levels were increased in cognitively unimpaired participants with abnormal Aβ-PET but normal tau-PET in the entorhinal cortex (Aβ-PET+/ tau-PET- group vs Aβ-PET-/ tau-PET- group: median, 2.2 pg/mL [interquartile range (IQR), 1.5-2.9 pg/mL] vs 0.7 pg/mL [IQR, 0.3-1.4 pg/mL]). Most cognitively unimpaired participants who were discordant for plasma P-tau217 and tau-PET were positive for plasma P-tau217 and negative for tau-PET (P-tau217+/tau-PET-: 36 [94.7%]; P-tau217-/tau-PET+: 2 [5.3%]). Event-based modeling of cross-sectional data predicted that in cognitively unimpaired participants and in those with mild cognitive impairment, both plasma and CSF P-tau217 would change before the tau-PET signal in the entorhinal cortex, followed by more widespread cortical tau-PET changes. When testing the association with global Aβ load in nonlinear spline models, both plasma and CSF P-tau217 were increased at lower Aβ-PET values compared with tau-PET measures. Among participants with normal baseline tau-PET, the rates of longitudinal increase in tau-PET in the entorhinal cortex were higher in those with abnormal plasma P-tau217 at baseline (median standardized uptake value ratio, 0.029 [IQR, -0.006 to 0.041] vs -0.001 [IQR, -0.021 to 0.020]; Mann-Whitney U, P = .02). Conclusions and relevance: In this cohort study, plasma P-tau217 levels were increased during the early preclinical stages of AD when insoluble tau aggregates were not yet detectable by tau-PET. Plasma P-tau217 may hold promise as a biomarker for early AD brain pathology.
  • Thumbnail Image
    Item
    Feasibility of a lung airway navigation system using fiber-Bragg shape sensing and artificial intelligence for early diagnosis of lung cancer
    (Public Library of Science, 2022-12-07) Gruionu, Lucian Gheorghe; Udriștoiu, Anca Loredana; Iacob , Andreea Valentina; Constantinescu, Cătălin; Stan, Răzvan; Gruionu, Gabriel; Medicine, School of Medicine
    Currently early diagnosis of malignant lesions at the periphery of lung parenchyma requires guidance of the biopsy needle catheter from the bronchoscope into the smaller peripheral airways via harmful X-ray radiation. Previously, we developed an image-guided system, iMTECH which uses electromagnetic tracking and although it increases the precision of biopsy collection and minimizes the use of harmful X-ray radiation during the interventional procedures, it only traces the tip of the biopsy catheter leaving the remaining catheter untraceable in real time and therefore increasing image registration error. To address this issue, we developed a shape sensing guidance system containing a fiber-Bragg grating (FBG) catheter and an artificial intelligence (AI) software, AIrShape to track and guide the entire biopsy instrument inside the lung airways, without radiation or electromagnetic navigation. We used a FBG fiber with one central and three peripheral cores positioned at 120° from each other, an array of 25 draw tower gratings with 1cm/3nm spacing, 2 mm grating length, Ormocer-T coating, and a total outer diameter of 0.2 mm. The FBG fiber was placed in the working channel of a custom made three-lumen catheter with a tip bending mechanism (FBG catheter). The AIrShape software determines the position of the FBG catheter by superimposing its position to the lung airway center lines using an AI algorithm. The feasibility of the FBG system was tested in an anatomically accurate lung airway model and validated visually and with the iMTECH platform. The results prove a viable shape-sensing hardware and software navigation solution for flexible medical instruments to reach the peripheral airways. During future studies, the feasibility of FBG catheter will be tested in pre-clinical animal models.
  • Thumbnail Image
    Item
    Pathogenesis of Pancreatic Cancer-related Diabetes Mellitus: Quo Vadis?
    (Wolters Kluwer, 2019-05) Korc, Murray; Medicine, School of Medicine
  • Thumbnail Image
    Item
    Symptoms of Women With High-Risk, Early-Stage Ovarian Cancer
    (Wolters Kluwer, 2022) Chan, John K.; Tian, Chunqiao; Kesterson, Joshua P.; Monk, Bradley J.; Kapp, Daniel S.; Davidson, Brittany; Robertson, Sharon; Copeland, Larry J.; Walker, Joan L.; Wenham, Robert M.; Casablanca, Yovanni; Spirtos, Nick M.; Tewari, Krishnansu S.; Bell, Jeffery G.; Obstetrics and Gynecology, School of Medicine
    Objective: To assess the presentation, characteristics, and prognostic significance of symptoms in patients with high-risk early-stage epithelial ovarian cancer. Methods: A retrospective chart review was performed on all patients enrolled in a phase III clinical trial (GOG 157). All patients had surgically staged, high-risk early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II). Chi-square and Kaplan-Meier estimates and Cox proportional hazards models were used for statistical analyses. Results: Of 419 patients evaluated for symptoms, 301 (72%) presented with one or more symptoms, and 118 (28%) were asymptomatic but had a mass found on examination. Forty percent had only one symptom, and 32% had more than one symptom. Among those with at least one symptom, the most common were abdominal and pelvic pain (31%), and increased girth or fullness (26%). Overall, 23% of patients with tumors 10 cm or smaller, 27% of patients with tumors larger than 10 cm to 15 cm, and 46% of patients with tumors larger than 15 cm had multiple symptoms (P<.001). There was no significant difference in presentation of symptoms based on age, stage, or histologic subtype. Symptoms at diagnosis were not associated with recurrence or survival. Conclusion: More than 70% of patients with high-risk early-stage, epithelial ovarian cancer present with one or more symptoms, with the most common being abdominal or pelvic pain. The proportion of women with symptoms and the number of symptoms increase with enlarging tumor size.
  • Thumbnail Image
    Item
    Understanding DNA Methylation patterns in Breast Cancer
    (Office of the Vice Chancellor for Research, 2015-04-17) Seby, Sandra; Pradhan, Meeta; Palakal, Mathew
    Breast Cancer is the most frequently diagnosed cancer among women worldwide. According to the estimates of the American Cancer Society, 231,840 new cases of invasive breast cancer will be diagnosed in US women in 2015. Early diagnosis of breast cancer relies on extensive understanding of the molecular mechanisms underlying its development and progression. In addition to the genetic and hormonal risk factors that are responsible for breast carcinogenesis, other factors such as life-styles, environmental and nutritional factors also plays a part in development of this complex disease. The study of these factors which modifies the genome without altering the DNA sequence is termed as cancer epigenetics. DNA methylation is an extensively studied epigenetic dysregulation which governs cell differentiation, and other aberrancies which can steer cells towards a malignant phenotype. This heritable, tissue- and species-specific DNA modification primarily occurs at cytosine-guanine (CpG) dinucleotides and often causes silencing of gene expression. Since altered DNA methylation patterns are commonly observed in various types of malignancies including Breast cancer, it is a potential target to investigate for diagnosis and prognosis of cancer. The main aim of our study was to identify DNA methylation pattern in Breast cancer patients and correlate it with the disease progression. We evaluated 5 Breast tumor samples and 2 Breast normal samples (Stages II and III) obtained from The Cancer Genome Atlas. The DNA from the samples were Bisulfite sequenced which provides the wholegenome coverage at a single-nucleotide resolution and is considered the gold-standard approach for quantitative measurement of DNA methylation level. The mapped bisulfite reads where processed to obtain the methylation ratio of all cytosine positions. The data was analyzed to identify the differentially methylated positions on all chromosomes. The results of our study shows that 97.3% of the differentially methylated positions overlap with intergenic regions, 0.1% in promoter regions and remaining in the exon and intronic regions. Out of 160803 differentially methylated positions, 139579 positions were hypo-methylated and 21224 were hyper-methylated positions. We observed that majority of the differentially methylated positions are were hypo-methylated which traditionally affects gene transcription. Highest number of hypo-methylated and hyper- methylated positions were observed on chromosome 1 and 5 respectively. As per our study NR5A2, BCAS3, PRR11, VMP1, PBX1 are the top 5 genes which are aberrantly methylated in Breast cancer patients.